Cough medicines containing pholcodine (PHO) are used to suppress unproductive coughs and have been available as non-prescription products in many countries worldwide for decades. Recently, concerns have been raised about the safety of these products based on a body of evidence which purports to show a relationship between the use of pholcodine and the incidence of anaphylactic reactions to anaesthetic drugs.
The striking historical difference in apparent rates of anaphylaxis to neuromuscular blocking agents (NMBAs) in Norway and Sweden was the original stimulus to develop the ‘pholcodine hypothesis’. At that time pholcodine was not available in Sweden but consumption in Norway was high. The finding that pholcodine was a potent stimulus to IgE production, and the apparent cross – reactivity of this IgE with suxamethonium, led some Scandinavian researchers to propose that consumption of pholcodine explained the observed difference in anaphylaxis incidence across this border between otherwise similar populations. Subsequent withdrawal of pholcodine containing preparations from the market in Norway was said to have led to a reduction of NMBA related anaphylaxis in that country.
This review examines factors affecting the risks of anaphylaxis to NMBAs during surgery and critically evaluates the evidence supporting the ‘pholcodine hypothesis’. Unresolved issues and gaps in the current evidence base supporting a role for pholcodine in these reactions are examined.
As well as studies to examine the possible association with phlocodine, further research may be needed into other possible mechanisms of IgE-mediated allergic anaphylaxis to NMBAs, in patients not previously exposed to them. Calls to restrict the availability of useful medicinal substances should be based on firm evidence of risk rather than associations with unproven causality.
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